Academic literature on the topic 'MNTB neurons'

Despite the peripheral and central immaturities that limit auditory processing in juvenile animals, they are able to lateralize sounds using binaural cues. This study explores a central mechanism that may compensate for these limitations during development. Interaural time and level difference processing by neurons in the superior olivary complex depends on synaptic inhibition from the medial nucleus of the trapezoid body (MNTB), a group of inhibitory neurons that is activated by contralateral sound stimuli. In this study, we examined the maturation of coding properties of MNTB neurons and found that they receive an inhibitory influence from the ipsilateral ear that is modified during the course of postnatal development. Single neuron recordings were obtained from the MNTB in juvenile (postnatal day 15–19) and adult gerbils. Approximately 50% of all recorded MNTB neurons were inhibited by ipsilateral sound stimuli, but juvenile neurons displayed a much greater suppression of firing as compared with those in adults. A comparison of the prepotential and postsynaptic action potential indicated that inhibition occurred at the presynaptic level, likely within the cochlear nucleus. A simple linear model of level difference detection by lateral superior olivary neurons that receive input from MNTB suggested that inhibition of the MNTB may expand the response of LSO neurons to physiologically realistic level differences, particularly in juvenile animals, at a time when these cues are reduced.

Genes Kcna1 and Kcna2 code for the voltage-dependent potassium channel subunits Kv1.1 and Kv1.2, which are coexpressed in large axons and commonly present within the same tetramers. Both contribute to the low-voltage–activated potassium current IKv1, which powerfully limits excitability and facilitates temporally precise transmission of information, e.g., in auditory neurons of the medial nucleus of the trapezoid body (MNTB). Kcna1-null mice lacking Kv1.1 exhibited seizure susceptibility and hyperexcitability in axons and MNTB neurons, which also had reduced IKv1. To explore whether a lack of Kv1.2 would cause a similar phenotype, we created and characterized Kcna2-null mice (−/−). The −/− mice exhibited increased seizure susceptibility compared with their +/+ and +/− littermates, as early as P14. The mRNA for Kv1.1 and Kv1.2 increased strongly in +/+ brain stems between P7 and P14, suggesting the increasing importance of these subunits for limiting excitability. Surprisingly, MNTB neurons in brain stem slices from −/− and +/− mice were hypoexcitable despite their Kcna2 deficit, and voltage-clamped −/− MNTB neurons had enlarged IKv1. This contrasts strikingly with the Kcna1-null MNTB phenotype. Toxin block experiments on MNTB neurons suggested Kv1.2 was present in every +/+ Kv1 channel, about 60% of +/− Kv1 channels, and no −/− Kv1 channels. Kv1 channels lacking Kv1.2 activated at abnormally negative potentials, which may explain why MNTB neurons with larger proportions of such channels had larger IKv1. If channel voltage dependence is determined by how many Kv1.2 subunits each contains, neurons might be able to fine-tune their excitability by adjusting the Kv1.1:Kv1.2 balance rather than altering Kv1 channel density.

Glial cell processes are part of the synaptic structure and sense spillover of transmitter, while some glial cells can even receive direct synaptic input. Here, we report that a defined type of glial cell in the medial nucleus of the trapezoid body (MNTB) receives excitatory glutamatergic synaptic input from the calyx of Held (CoH). This giant glutamatergic terminal forms an axosomatic synapse with a single principal neuron located in the MNTB. The NG2 glia, as postsynaptic principal neurons, establish synapse-like structures with the CoH terminal. In contrast to the principal neurons, which are known to receive excitatory as well as inhibitory inputs, the NG2 glia receive mostly, if not exclusively, α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptor–mediated evoked and spontaneous synaptic input. Simultaneous recordings from neurons and NG2 glia indicate that they partially receive synchronized spontaneous input. This shows that an NG2+ glial cell and a postsynaptic neuron share presynaptic terminals.

The medial nucleus of the trapezoid body (MNTB) is an important source of inhibition during the computation of sound location. It transmits fast and precisely timed action potentials at high frequencies; this requires an efficient calcium clearance mechanism, in which plasma membrane calcium ATPase 2 (PMCA2) is a key component. Deafwaddler ( dfw 2J) mutant mice have a null mutation in PMCA2 causing deafness in homozygotes ( dfw 2J/ dfw 2J) and high-frequency hearing loss in heterozygotes (+/ dfw 2J). Despite the deafness phenotype, no significant differences in MNTB volume or cell number were observed in dfw 2J homozygous mutants, suggesting that PMCA2 is not required for MNTB neuron survival. The MNTB tonotopic axis encodes high to low sound frequencies across the medial to lateral dimension. We discovered a cell size gradient along this axis: lateral neuronal somata are significantly larger than medially located somata. This size gradient is decreased in +/ dfw 2J and absent in dfw 2J/ dfw 2J. The lack of acoustically driven input suggests that sound-evoked activity is required for maintenance of the cell size gradient. This hypothesis was corroborated by selective elimination of auditory hair cell activity with either hair cell elimination in Pou4f3 DTR mice or inner ear tetrodotoxin (TTX) treatment. The change in soma size was reversible and recovered within 7 days of TTX treatment, suggesting that regulation of the gradient is dependent on synaptic activity and that these changes are plastic rather than permanent. NEW & NOTEWORTHY Neurons of the medial nucleus of the trapezoid body (MNTB) act as fast-spiking inhibitory interneurons within the auditory brain stem. The MNTB is topographically organized, with low sound frequencies encoded laterally and high frequencies medially. We discovered a cell size gradient along this axis: lateral neurons are larger than medial neurons. The absence of this gradient in deaf mice lacking plasma membrane calcium ATPase 2 suggests an activity-dependent, calcium-mediated mechanism that controls neuronal soma size.

We describe neurons in two nuclei of the superior olivary complex that display differential sensitivities to sound duration. Single units in the medial nucleus of the trapezoid body (MNTB) and superior paraolivary nucleus (SPON) of anesthetized rats were studied. MNTB neurons produced primary-like responses to pure tones and displayed a period of suppressed spontaneous activity after stimulus offset. In contrast, neurons of the SPON, which receive a strong glycinergic input from MNTB, showed very little or no spontaneous activity and responded with short bursts of action potentials after the stimulus offset. Because SPON spikes were restricted to the same time window during which suppressed spontaneous activity occurs in the MNTB, we presume that SPON offset activity represents a form of postinhibitory rebound. Using characteristic frequency tones of 2- to 1,000-ms duration presented 20 dB above threshold, we show that the profundity and duration of the suppression of spontaneous activity in MNTB as well as the magnitude and first spike latency of the SPON offset response depend on stimulus duration as well as on stimulus intensity, showing a tradeoff between intensity and duration. Pairwise comparisons of the responses to stimuli of various durations revealed that the duration sensitivity in both nuclei is sharpest for stimuli <50 ms.

We have investigated the fundamental properties of central auditory glycinergic synapses in early postnatal development in normal and congenitally deaf ( dn/dn) mice. Glycinergic miniature inhibitory postsynaptic currents (mIPSCs) were recorded using patch-clamp methods in neurons from a brain slice preparation of the medial nucleus of the trapezoid body (MNTB), at 12-14 days postnatal age. Our results show a number of significant differences between normal and deaf mice. The frequency of mIPSCs is greater (50%) in deaf versus normal mice. Mean mIPSC amplitude is smaller in deaf mice than in normal mice (mean mIPSC amplitude: deaf, 64 pA; normal, 106 pA). Peak-scaled fluctuation analysis of mIPSCs showed that mean single channel conductance is greater in the deaf mice (deaf, 64 pS; normal, 45 pS). The mean decay time course of mIPSCs is slower in MNTB neurons from deaf mice (mean half-width: deaf, 2.9 ms; normal, 2.3 ms). Light- and electron-microscopic immunolabeling results showed that MNTB neurons from deaf mice have more (30%) inhibitory synaptic sites (postsynaptic gephyrin clusters) than MNTB neurons in normal mice. Our results demonstrate substantial differences in glycinergic transmission in normal and congenitally deaf mice, supporting a role for activity during development in regulating both synaptic structure (connectivity) and the fundamental (quantal) properties of mIPSCs at central glycinergic synapses.

Neurons in the medial nucleus of the trapezoid body (MNTB) are well known for their prominent excitatory inputs, mediated by the calyx of Held. Less attention has been paid to the prominent inhibitory inputs that MNTB neurons also receive. Because of their auditory nature, both excitatory and inhibitory synapses are highly active in vivo. These high levels of activity are known to reduce excitatory synaptic currents considerably, such that in vivo synaptic currents produced by the calyx are smaller than typically measured in standard brain slice experiments. The goal of this study was to investigate the properties of the inhibitory inputs in the Mongolian gerbil ( Meriones unguiculatus) under activity levels that correspond to those in the intact brain to facilitate a direct comparison between the two inputs. Our results suggest that inhibitory inputs to MNTB are largely mediated by a fast and phasic glycinergic component, and to a lesser degree by a GABAergic component. The glycinergic component can sustain prolonged high levels of activity. Even when challenged with stimulus patterns consisting of thousands of stimuli over tens of minutes, glycinergic inputs to MNTB maintain large conductances and fast decays and even facilitate substantially when the stimulation frequency is increased. The inhibition is mediated by a relatively small number of independent input fibers. The data presented here suggest that inhibitory inputs to MNTB sustain high levels of activity and need to be considered for a full understanding of mechanisms underlying processing of auditory information in MNTB.

1. The physiological properties of cells in the superior olivary complex (SOC) were studied in 400-microns brain slices taken through the mouse auditory brain stem. Coronal sections were prepared from fresh brain tissue and were placed fully submerged in an oxygenated saline solution. The boundaries of the medial nucleus of the trapezoid body (MNTB), the lateral superior olive (LSO), and the fibers of the trapezoid body were visualized through a dissecting microscope, and micropipettes filled with 4 M potassium acetate were inserted into the LSO or MNTB. 2. Bipolar stimulating electrodes were placed along the trapezoid body usually at the midline decussation and at a location just lateral to the LSO. This arrangement allowed for stimulation of the trapezoid body both contralateral and ipsilateral to the SOC. Synaptic potentials were elicited by delivering brief (0.1 ms) current pulses to the fibers of the trapezoid body. In some cases the integrity of the fibers was confirmed by transport of horseradish peroxidase (HRP) after extracellular microinjections at various locations along the pathway. The HRP reaction product revealed active transport within the trapezoid body and characteristic synaptic and terminal morphology in the MNTB and LSO. The MNTB contained primarily large-diameter fibers terminating in specialized endings (the calyces of Held), whereas the LSO contained mainly small-diameter fibers and punctate terminal boutons. 3. Membrane characteristics of cells in MNTB and LSO were determined by injecting current into the cell and measuring the corresponding voltage change. Neurons in LSO exhibited a roughly linear relation between voltage and intracellularly injected current. Negative current resulted in a graded hyperpolarization of the cell membrane, and positive current resulted in a graded depolarization that led to the production of action potentials. The number of action potentials was directly related to the strength of the current injected. In contrast, the neurons in MNTB had current-voltage relations that were strongly nonlinear around resting potential. The injection of negative current led to graded hyperpolarization, but injection of positive current produced a limited depolarization that resulted in either a single large action potential or an action potential followed by several spikes with greatly reduced amplitude. 4. Excitatory postsynaptic potentials (EPSPs) could be elicited in LSO by ipsilateral stimulation of the trapezoid body and in MNTB by contralateral stimulation. In response to repeated stimulation, some cells in LSO exhibited temporal summation, that is, a series of slightly subthreshold current pulses produced postsynaptic potentials that combined to elicit action potentials.(ABSTRACT TRUNCATED AT 400 WORDS)

In vivo recordings from postsynaptic neurons in the medial nucleus of the trapezoid body (MNTB), an auditory brain stem nucleus, show that acoustic stimulation produces a burst of spikes followed by a period of hyperpolarization and suppressed spiking activity. The underlying mechanism for this hyperpolarization and reduced spiking is unknown. Furthermore, the mechanisms that control excitability and resting membrane potential are not fully determined for these MNTB neurons. In this study we investigated the excitability of principal neurons from the MNTB after high-frequency afferent fiber stimulation, using whole cell recordings from postnatal day 15–17 rat brain stem slices. We found that Na+-K+-ATPase activity mediates a progressive hyperpolarization during a prolonged tetanic train and a posttetanic hyperpolarization (PTH) at the end of the train, when postsynaptic action potentials failed to fire. Raising the temperature to more physiological levels (from 22 to 35°C) depolarized the resting membrane potential of both presynaptic and postsynaptic cells and decreased the latency of action potential firing during PTH. Higher temperatures also reduced the presynaptic calyx action potential failure rates by 50% during presynaptic PTH, thus increasing the safety-factor for presynaptic spiking. The effect of temperature on hyperpolarization-activated cation current ( Ih) is reflected in the resting potential at both pre- and postsynaptic neurons. We thus propose that temperature-sensitive Na+-K+-ATPase activity and Ih contribute to set the resting membrane potential and produce a brief period of suppressed spiking (or action potential failures) after a prolonged high-frequency afferent tetanus.

Interaural intensity differences are analyzed in neurons of the lateral superior olive (LSO) by integration of an inhibitory input from the medial nucleus of the trapezoid body (MNTB), activated by sound from the contralateral ear, with an excitatory input from the ipsilateral cochlear nucleus. The early postnatal refinement of this inhibitory MNTB-LSO projection along the tonotopic axis of the LSO has been extensively studied. However, little is known to what extent physiological changes at these inputs also occur after the onset of sound-evoked activity. Using whole-cell patch-clamp recordings of LSO neurons in acute brain stem slices, we analyzed the developmental changes of inhibitory synaptic currents evoked by MNTB fiber stimulation occurring after hearing onset. We compared these results in gerbils and mice, two species frequently used in auditory research. Our data show that neither the number of presumed input fibers nor the conductance of single fibers significantly changed after hearing onset. Also the amplitude of miniature inhibitory currents remained constant during this developmental period. In contrast, the kinetics of inhibitory synaptic currents greatly accelerated after hearing onset. We conclude that tonotopic refinement of inhibitory projections to the LSO is largely completed before the onset of hearing, whereas acceleration of synaptic kinetics occurs to a large part after hearing onset and might thus be dependent on proper auditory experience. Surprisingly, inhibitory input characteristics, as well as basic membrane properties of LSO neurons, were rather similar in gerbils and mice.

De nombreuses villes d’Asie du Sud-Est subissent de graves inondations liées d’une part à l’intensité croissante des précipitations et d’autre part à une urbanisation rapide souvent due à une planification urbaine non maitrisée. L'évaluation quantitative des risques d'inondation nécessite deux éléments essentiels : (1) un modèle numérique de terrain (MNT) haute définition, et (2) une chronologie de précipitations la plus longue possible. Un MNT haute définition est à la fois coûteux et long à acquérir. Les chronologies de précipitations longues sont fréquemment indisponibles dans de nombreux sites et ne présentent pas toujours une durée suffisante pour une définition pertinente des valeurs extrêmes. Cette thèse présente une approche opérationnelle pour générer des MNT haute définition et suggère une stratégie pour définir des pluies extrêmes en dehors de chronologies de précipitations longues. Des données pour la production des MNT issues de capteurs satellitaires - mission SRTM (Shuttle Radar Topography Mission) et images multi spectrales Sentinel 2 - ont été utilisées et mises en œuvre. Un réseau de neurones artificiels (ANN) est utilisé afin d'améliorer la qualité du MNT. Dans la phase d’apprentissage du réseau de neurones, la qualité des MNE utilisés comme référence est essentielle et conditionne la performance de l’outil dans son application ultérieure. A la suite de cet apprentissage, le réseau de neurones peut être mis en œuvre pour générer, à faible coût, des MNT haute résolution dans des secteurs où les données sont partiellement indisponibles.Les performances de la méthode d’amélioration du MNT sont évaluées dans des différents secteurs caractérisés par des occupations du sol variées (secteur urbain dense, secteurs boisés par exemple) et dans différents pays (Nice, France, Singapour, Jakarta, Indonésie). La qualité des résultats est analysée avec différents indicateurs tels que les diagrammes de dispersion, la clarté visuelle, l’erreur quadratique moyenne (RMSE) et l’adéquation avec les réseaux de drainage réels. Le MNT issu des données SRTM améliorées montre (1) une qualité nettement supérieure au MNT initial puisque le RMSE passe de 34% à 57% du RMSE ; (2) la clarté visuelle est largement améliorée ; et (3) le réseau de drainage calculé correspond davantage au réseau réel. La production de ce MNT amélioré permet une meilleure modélisation des processus d’inondation et augmente la qualité des résultats des simulations hydrauliques. Des données de précipitation issues d'un Modèle Climatologique Régional (RCM) haute résolution spatiale ainsi que des prévisions issues de données ERA-Interim (WRF / ERAI) ont été extraites, analysées et comparées avec les observations haute résolution enregistrées à Singapour. Les comparaisons ont également été effectuées avec les courbes Intensité-Durée-Fréquence (IDF) qui sont utilisées pour l'évaluation des risques d'inondation. Les résultats sont très satisfaisants et valident les données produites par le modèle régional. Cette validation permet d’utiliser les données pluviométriques issues du modèle régional pour le site de la métropole de Jakarta (Indonésie) où les enregistrements pluviométriques ne sont pas disponibles pour la production des courbes IDF.Un modèle hydraulique détaillé a été construit avec le système de modélisation MIKE 21 pour toute la métropole de Jakarta à partir d’un MNT amélioré et des précipitations associées à des périodes de retour de 50 et 100 ans. Des cartes d’inondation ont été générées et sont utilisées par les services gestionnaires. Cet exemple démontre que les nouvelles méthodes et approches proposées dans cette thèse sont pertinentes pour produire une évaluation des risques d’inondation pertinente lorsque des données locales (MNT haute résolution et données pluviométriques sur une période longue) sont insuffisantes ou indisponibles
Many urban cities in Southeast Asia witness severe flooding associated to increasing rainfall intensity and rapid urbanization often due to poor urban planning. Two important inputs required in flood hazard assessment are: (1) high accuracy Digital Elevation Model (DEM), and (2) long rainfall record. High accuracy DEM is both expensive and time consuming to acquire. Long rainfall records for areas of interest are often not available or not sufficiently long to determine the probable extremes. This thesis presents a notably cost-effective and efficient approach to derive high accuracy DEM, and suggests proxies for long rainfall data.DEM data from a publicly accessible satellite, Shuttle Radar Topography Mission (SRTM), and Sentinel 2 multispectral imagery are selected and used to train the Artificial Neural Network (ANN) to improve the quality of the DEM. In the training of ANN, high quality observed DEM is the key leading to a well-trained ANN. The trained ANN will then be ready to efficiently and effectively generate high quality DEM, at low cost, for places where DEM data is not available.The performance of the DEM improvement scheme is evaluated in places of various land-use types (e.g. dense urban city, forested areas), and in different countries (Nice, France; Singapore; Jakarta, Indonesia) through various matrices, e.g. whenever possible visual clarity, scatter plots, Root Mean Square Error (RMSE) and/or drainage networks. The DEM resulting from the latest version of improved SRTM (iSRTM_v2 DEM) shows (1) significantly better than the original SRTM DEM, a 34 % to 57 % RMSE reduction; (2) the visual clarity is so much clearer as well; and (3) much closer drainage network with the actual. The much improved DEM allows flood modelling to proceed with high confidence.Rainfall data resulting from a high spatial resolution Regional Climate Model (RCM), Weather Research and Forecasting driven by ERA-Interim (WRF/ERAI) dataset, is extracted, analyzed, and compared its accuracy with high quality observed rainfall data of Singapore. The comparisons are performed, among others, on their Intensity-Duration-Frequency (IDF) curves, the essential design curves for flood risk assessment; they matched quite well. The rainfall data (from the RCM) are then used as proxies for Greater Jakarta (Indonesia), where no rainfall data made available, to derive the IDF curves required for the flood analysis.MIKE 21 Flow Model Flexible Mesh (MIKE 21 FM) is applied to Greater Jakarta, with input data from the above mentioned much improved DEM and precipitation proxy data, for flood simulations of 2 return periods (50- and 100-years). Finally flood maps are generated. This demonstrates the applications of the approaches/methodologies, proposed in this thesis, on catchments where most essential data for flood risk assessment (high resolution and high accuracy DEM and long and high accuracy rainfall data) are not available.This thesis should be of interest to readers in the areas of remote sensing, artificial intelligence and flood management, especially for the policy makers in proposing relevant flood mitigation measures under climate change with increasing devastating flood damages and casualties